NM_001370259.2(MEN1):c.830C>A (p.Pro277His) AND Multiple endocrine neoplasia, type 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 10, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000471154.9

Allele description [Variation Report for NM_001370259.2(MEN1):c.830C>A (p.Pro277His)]

NM_001370259.2(MEN1):c.830C>A (p.Pro277His)

Gene:

MEN1:menin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_001370259.2(MEN1):c.830C>A (p.Pro277His)

HGVS:

NC_000011.10:g.64807093G>T
NG_008929.1:g.9202C>A
NG_033040.1:g.1149C>A
NM_000244.4:c.845C>A
NM_001370251.2:c.830C>A
NM_001370259.2:c.830C>AMANE SELECT
NM_001370260.2:c.830C>A
NM_001370261.2:c.830C>A
NM_001370262.2:c.725C>A
NM_001370263.2:c.725C>A
NM_130799.3:c.830C>A
NM_130800.3:c.845C>A
NM_130801.3:c.845C>A
NM_130802.3:c.845C>A
NM_130803.3:c.845C>A
NM_130804.3:c.845C>A
NP_000235.3:p.Pro282His
NP_001357180.2:p.Pro277His
NP_001357188.2:p.Pro277His
NP_001357189.2:p.Pro277His
NP_001357190.2:p.Pro277His
NP_001357191.2:p.Pro242His
NP_001357192.2:p.Pro242His
NP_570711.1:p.Pro277His
NP_570711.2:p.Pro277His
NP_570712.2:p.Pro282His
NP_570713.2:p.Pro282His
NP_570714.2:p.Pro282His
NP_570715.2:p.Pro282His
NP_570716.2:p.Pro282His
LRG_509t2:c.830C>A
LRG_509:g.9202C>A
LRG_509p2:p.Pro277His
NC_000011.9:g.64574565G>T
NM_130799.2:c.830C>A

Protein change:

P242H

Links:

dbSNP: rs1060499973

NCBI 1000 Genomes Browser:

rs1060499973

Molecular consequence:

NM_000244.4:c.845C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370251.2:c.830C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370259.2:c.830C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370260.2:c.830C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370261.2:c.830C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370262.2:c.725C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370263.2:c.725C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130799.3:c.830C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130800.3:c.845C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130801.3:c.845C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130802.3:c.845C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130803.3:c.845C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130804.3:c.845C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Multiple endocrine neoplasia, type 1 (MEN1)
Synonyms:: MEA I; MEN I; Endocrine adenomatosis multiple; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007540; MeSH: D018761; MedGen: C0025267; Orphanet: 652; OMIM: 131100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000541179	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12016470, 21819486, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000541179

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 10, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic screening for MEN1 mutations in families presenting with familial primary hyperparathyroidism.

Perrier ND, Villablanca A, Larsson C, Wong M, Ituarte P, Teh BT, Clark OH.

World J Surg. 2002 Aug;26(8):907-13. Epub 2002 May 21.

PubMed [citation]

PMID:: 12016470

Correlation of mutant menin stability with clinical expression of multiple endocrine neoplasia type 1 and its incomplete forms.

Shimazu S, Nagamura Y, Yaguchi H, Ohkura N, Tsukada T.

Cancer Sci. 2011 Nov;102(11):2097-102. doi: 10.1111/j.1349-7006.2011.02055.x. Epub 2011 Sep 1.

PubMed [citation]

PMID:: 21819486

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000541179.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 277 of the MEN1 protein (p.Pro277His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with MEN1-associated endocrine tumors and/or primary hyperparathyroidism (PMID: 12016470; Invitae). ClinVar contains an entry for this variant (Variation ID: 403801). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function. Experimental studies have shown that this missense change affects MEN1 function (PMID: 21819486). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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